Otitis media (OM) is a worldwide pediatric health care problem. In physician office practices in the United States, it is the most common diagnosis made in children under 15 years of age. Using the twin study approach, we have recently demonstrated that time with middle ear effusion (MEE), number of episodes of MEE and number of episodes of acute otitis media (AOM) have a strong genetic component. The point estimate of heritability of time with MEE was 0.73. While there is significant evidence that susceptibility to recurrent/persistent OM is largely genetically determined, the specific genes which confer susceptibility are unknown. Our overall research strategy to identify genes underlying OM is to apply a three-stage study design that will allow us to balance cost efficiency with statistical power to detect OM genes. Five hundred pairs of siblings with a history of tympanostomy tube insertion (affected), their parent(s) and available non-affected full siblings will be recruited. A blood sample will be obtained from each subject for genotyping. The first stage will be to perform a 10 cM genome-scan in affected pairs of siblings and their parent(s). At this stage we will use a relatively generous significance criterion equivalent to a LOD of about 1.0 to identify chromosomal regions for further studies which will consist of a high density scan (approximately 1 cM) in the positive regions from the first stage. For this high-density scan a stringent significance criterion will be applied. Finally, we will use family based association/linkage disequilibrium analysis (TDT) of single nucleotide polymorphisms within positional candidate genes to identify specific genes that influence susceptibility to OM.The present study proposes to identify the genes that play a part in the development of recurrent/persistent OM. This may enable us to better understand the pathophysiology of OM and thus develop better methods for its prevention and treatment.